Long-term use of methotrexate by oncologists for maintenance therapy of acute lymphocytic leukemia and palliation of certain solid tumors, and by dermatologists for control of refractory psoriasis, has frequently been associated with serious lesions of the liver and lungs. Our preliminary toxicologic studies on mice and rats thus far have indicated that some rats, on selected schedules, develop hepatic and pulmonary lesions comparable to human ones, thus providing a model for subsequent work. Further, we have elicited suggestive evidence that concomitant administration of choline to the rats may vitiate to a considerable extent the liver damage without affecting the inhibitory influence of MTX on lymphatic and hematopoietic tissues. We plan to expand these studies in rats to confirm our initial observations. Finally, should choline prove effective in rats, its value in man will be assayed.